This proposal involves the synthesis of several new analogs of methotrexate, an anti-neoplastic agent. On the basis of prior metabolic studies, these analogs (7-substituted derivatives) are predicted to be less toxic than methotrexate at a high dose regimen. The research will be carried out primarily by the principal investigator and junior college students who have demonstrated a potential or capability for biomedically related fields. Synthetic schemes based on procedures that have already been reasonably developed will be utilized. At the completion of the synthesis, analogs will be submitted for biological activity studies.